Breast cancer and antibiotic use?

Julia Draznin Maltzman, MD The Abramson Cancer Center of the University of Pennsylvania

What's all the fuss?

For years, doctors have been telling women that their chances of getting breast cancer may be related to genetics, previous radiation exposure, or possibly influenced by their reproductive choices. Risk of developing breast cancer is increased if a woman chooses to have her first born after the age of thirty or if she chooses never to have children at all. Could there be other reasons, medical or otherwise, why women may be predisposed to getting this disease? The link between viruses and cancer is well known and accepted. These include diseases such as Human Papilloma Virus (HPV) and cervical as well as oral cancer, Epstein-Barr Virus (EBV) and certain types of lymphoma as well as nasopharyngeal cancer (a type of cancer of the head and neck), and Human Immunodeficiency Virus (HIV) that is implicated in many lymphomas and skin cancers such as Kaposis Sarcoma. However, the link between antibiotics and cancer is more subtle.

Over twenty years ago, in the journal The Lancet, investigators alluded to the possibility that antibiotic use may somehow be related to the development of cancer. Many years later, a Finnish group looked into this disconcerting possibility. Looking at nearly 10,000 women, the study did suggest that there was indeed a link between the two. However, their study is often criticized for its poor design and execution. More recently, Dr. Christine Velicer from the Department of Epidemiology at the University of Washington, Seattle, examined the links between antibiotic use among women and the development of breast cancer in a rigorous manner. This study was published in the February 18th edition of the Journal of the American Medical Association and received much publicity from the press.

This population-based control study that compared over 2,000 women with newly diagnosed breast cancer with almost 8,000 healthy controls who were members of the same, large, non-profit health insurance plan. Breast cancer patients were identified from the SEER data (Surveillance, Epidemiology, and End Results). Information on antibiotic use for both cancer patients and healthy controls was obtained from computerized pharmacy records. After a thorough analysis, the study found that the more days over the preceding years a woman took antibiotics, the higher her risk of developing breast cancer. Specifically, women who took antibiotics for more than 500 days, or had more than 25 prescriptions, over an average period of 17 years, had more than twice the risk of developing breast cancer as women who did not take any antibiotics. These findings were found to be statistically significant. No specific type or class of antibiotic that was any more or less likely to contribute to this risk. Increasing cumulative days of antibiotic use was found to be statistically significantly associated with death due to the disease. The risk was smaller for women who took antibiotics for fewer than 500 days, but still present. Women who had between one and 25 prescriptions over this time period were one and a half times more likely to be diagnosed with breast cancer than women who did not take any antibiotics.

Investigators examined how these two groups of women differed and found that women with breast cancer had a higher number of health care visits in the preceding year, were more likely to be premenopausal, and had their first pregnancy after the age of thirty. Not surprisingly, women with breast cancer also tended to have first-degree family members with this disease.

Perspective

To put these results in perspective, we should consider the recently well-publicized debate over the risk of developing breast cancer in women who take hormone replacement therapy after cessation of menstrual periods. The presumed risk of developing breast cancer from hormone replacement therapy for postmenopausal women is estimated to be about a 30 to 40 percent increase in risk. This study reported a doubling (50%) in risk for those women who took antibiotics.

Discussion

Experts quickly caution that women should not stop taking antibiotics. Antibiotics are prescribed for a large array of conditions including ear infections, respiratory infections, urinary tract infections, sinus infections, and acne. Although this study noted an association between cancer and antibiotic use, there is no clear cause and effect established. Women who were prescribed antibiotics for active infections should definitely continue using them according to the specification of their physicians.

The authors of the study initially thought that perhaps women who seek antibiotics are more likely to visit their physicians on a regular basis and get screened for malignancies and therefore more likely to be diagnosed. However, even after excluding this factor, the association between antibiotic use and breast cancer remained strong.

The study offered a possible explanation for their observation. Antibiotics affect the bacteria in the gut, and in many ways interfere with the natural balance that exist in the intestines. By eliminating a certain population of bacteria within the intestine, food metabolism and digestion is affected. It is conceivable that foods high in antioxidants, thought to protect against cancer, cannot be metabolized and digested properly if the gut flora is altered. The rational being that if protective nutrients cannot be absorbed then the risks of developing a malignancy are higher.

Other scientists offered the possibility that antibiotics may affect the body's own immune system and inflammatory response. When the immune and the inflammatory systems are revved up, there is a sudden release of cytokines into the blood stream. Cytokines act as intercellular mediators (much like hormones) and have many different affects on cell growth, differentiation, and spread. One could hypothesize that frequent surges in cytokines in an individual's body may lead to the potentiation of cellular pathways that could predispose to cancer development. It is also possible that it is not the antibiotics that are stimulating cytokine release, but rather the infection itself for which the antibiotics are sought. For example, it is not unusual that a woman may be on long-term antibiotics for acne. Some forms of acne can be severe and result in a chronic inflammatory state. Some have argued that it is precisely this chronic inflammation that may predispose to the development of cancer.

Another group of experts noted that perhaps women with frequent needs for antibiotics have many health problems and may be susceptible to all kinds of diseases, including cancer. In other words, some women are biologically predisposed to get breast cancer for other reasons such as a weak immune system or hormonal imbalances. (Acne, for example, can be due to hormonal imbalances – which is why it is often seen in teenagers who have great cycles of hormones. Acne, in turn, is a common reason for antibiotic use.) Thus, it is the resultant weak immune systems and hormonal imbalances may cause the increased risk for both breast cancer and the frequent infections requiring antibiotic treatment.

Investigators have much to explore and to consider. The causes of breast cancer remain elusive, but this study has provided some insight into various possibilities: baseline immunosuppression, hormonal imbalance, altered gut flora, a chronic inflammatory state, or perhaps, the antibiotics themselves.

Disbelievers

The fact that not one single type (or class) of antibiotic was more strongly associated with the risk of developing breast cancer has fueled debate for some skeptics. It is difficult to accept that all antibiotics with such widely differing mechanisms of action, and derivations, contribute equally to the risk of developing breast cancer.

Provocative

If, in the end, it turns out that antibiotics do not increase the risk of developing breast cancer, these results are still very significant. These findings could lead to the discovery of what it is about this cohort of women who developed breast cancer.

While this issue is resolving, it serves as further evidence for primary care physicians, pediatricians, family doctors, etc, to use antibiotics prudently – reserving them for those who really need them. However, those that truly need antibiotics, should not avoid them for fear of getting breast cancer.